Increased surfactant protein-D and foamy macrophages in smoking-induced mouse emphysema
Increased surfactant protein-D and foamy macrophages in smoking-induced mouse emphysema
复制标题
DOI：
10.1111/j.1440-1843.2006.01009.x
复制
发表时间：
2007-03-01
期刊：
影响因子：
6.9
通讯作者：
Kubota, Isao
中科院分区：
文献类型：
--
作者：
Hirama, Noriyuki;Shibata, Yoko;Kubota, Isao
COPD 的分子机制仍不清楚。表面活性蛋白-D (SP-D) 缺陷小鼠的肺部表现出肺气肿和过多的泡沫状巨噬细胞。本研究旨在阐明 SP-D 和泡沫状巨噬细胞在吸烟引起的小鼠肺气肿中的作用。将 20 只 B6C3F1 小鼠暴露于香烟烟雾中（2 支香烟/天/小鼠，持续 6 个月）。处死小鼠，对7只小鼠进行福尔马林固定、石蜡包埋的肺切片，对6只小鼠进行BAL，并用7只小鼠制作肺匀浆。在体外研究中，用SP-D表达质粒转导A549细胞，并用香烟烟雾提取物处理以评估细胞活力。长期暴露于香烟烟雾会诱发小鼠肺气肿。观察到基质金属蛋白酶-9和-12的表达增加，并且泡沫状肺泡巨噬细胞在暴露于烟雾的肺部中积聚。 BAL 细胞的免疫染色显示基质金属蛋白酶 12 的主要来源是泡沫状肺泡巨噬细胞。此外，肺气肿肺中 SP-D 升高。肺气肿肺中转录因子 Fra-1、junB 和 C/EBP beta（诱导 SP-D）的表达显着升高。 A549细胞中SP-D基因的体外表达延长了暴露于香烟烟雾冷凝物后的细胞存活率。泡沫状肺泡巨噬细胞的积累可能在吸烟引起的肺气肿的发生中起关键作用。 SP-D 增加可能在吸烟引起的肺气肿的发展中发挥保护作用，部分是通过防止肺泡细胞死亡。
The molecular mechanisms underlying COPD remain undetermined. The lungs of surfactant protein-D (SP-D) deficient mice show emphysema and an excessive number of foamy macrophages. This study aims to elucidate roles of SP-D and foamy macrophages in smoking-induced mouse emphysema.Twenty B6C3F1 mice were exposed to cigarette smoke (2 cigarettes/day/mouse for 6 months). The mice were killed, and formalin-fixed, paraffin-embedded lung sections were carried out on seven mice, BAL was carried out on six mice, and seven mice were used to make lung homogenates. In in vitro studies, A549 cells were transduced with the SP-D expression plasmid and treated with cigarette smoke extract to evaluate cell viability.Emphysema was induced in the mice by chronic cigarette smoke exposure. Increased expression of matrix metalloproteinase-9 and -12 was observed, and foamy alveolar macrophages accumulated in the smoke-exposed lungs. Immunostaining of BAL cells revealed the major source of matrix metalloproteinase-12 to be foamy alveolar macrophages. Furthermore, SP-D was elevated in emphysema lungs. Expression of transcription factors, Fra-1, junB and C/EBP beta (which induce SP-D) were significantly elevated in emphysema lungs. The in vitro expression of SP-D gene in A549 cells prolonged cell survival following exposure to cigarette smoke condensate.The accumulation of foamy alveolar macrophages may play a key role in the development of smoking-induced emphysema. Increased SP-D may play a protective role in the development of smoking-induced emphysema, in part by preventing alveolar cell death.